The blood vessels in a mouse's lungs are illuminated with a technique developed by faculty and staff at Washington University School of Medicine in St. Louis. The largest vessels glow scarlet and the smallest are blue. This 40-second video was named a 2017 BioArt winner.

A lacy network of red, blue, gold and green strands rotates hypnotically in a 40-second video, tracing the many blood vessels in a mouse’s lungs. The video, created by faculty and staff at Washington University School of Medicine in St. Louis, was named a winner of the 2017 BioArt competition in December. The annual contest is held by the Federation of American Societies for Experimental Biology.

The video was created by James Fitzpatrick, PhD, scientific director; Matthew Joens, PhD, a staff scientist; and Daniel Geanon, a research assistant, at the university’s Center for Cellular Imaging, in collaboration with David Ornitz, MD, PhD, the Alumni Endowed Professor of Developmental Biology, and Kel Vin Woo, MD, PhD, a clinical fellow in pediatrics.

Apart from its sheer intricate beauty, the image is valuable because it provides insight into a potentially fatal illness that plagues premature babies: hypoxia-induced pulmonary hypertension, or high blood pressure in the lungs caused by lack of oxygen.

Half a million babies are born prematurely in the United States every year, many of them before their lungs have developed the soapy liquid lining that makes breathing easy. The struggle to breathe with immature lungs creates a low-oxygen environment that can lead to pulmonary hypertension. Up to half of premature infants with both immature lungs and pulmonary hypertension die within two years of diagnosis. There are no therapies proven to prevent or treat pulmonary hypertension in premature infants.

To help such babies, Woo and Ornitz wanted to study how chronic exposure to low oxygen – a condition similar to the one experienced by preemies – damages the blood vessels in the lungs. To do so, they needed a detailed map of all the blood vessels, even the tiniest capillaries.

At the Center for Cellular Imaging, Fitzpatrick and his staff have been developing X ray-based methods of imaging animals down to the thinnest tissues. The technique involves injecting a tracing agent into a vein and letting it circulate throughout the body before imaging. The X-rays reflect off the tracing agent, lighting up each blood vessel.

But for Woo and Ornitz’s purposes, the standard tracing agent wouldn’t work because it is too thick to get into the capillaries, leaving them invisible.

“Matt Joens came up with the idea of using a concentrated gold nanoparticule emulsion to fill the vasculature,” said Fitzpatrick, who is also an associate professor of neuroscience, and of cell biology and physiology.

The nanoparticles slip in among the water molecules in the blood and dissolve without increasing the blood pressure. Using Joens’ novel technique, the researchers generated the winning video.

“The traditional way to do this kind of study is to slice the lungs into sections, and count the vessels and measure their width slice by slice,” Woo said. “It’s time-consuming, tedious and really just an estimation because we are taking a random sample. This new imaging tool gives us a way to quantify the vessels in an entire lung using computational software.”

The vibrant colors in the video correlate with the size of the blood vessels; the largest are scarlet, and the smallest are blue. The color coding provides researchers with clues to understand – and maybe one day treat ­– hypoxia-induced pulmonary hypertension.

Fitzpatrick and Joens are writing a manuscript describing their new imaging technique. In the meantime, the video that so strikingly depicts the power of their method is on display, along with the 11 other winners of the BioArt competition, at the National Institutes of Health (NIH) in Bethesda, Md. This is the second year in a row that an image submitted by Fitzpatrick and Joens has been named a winner of the BioArt competition.

Tamara Bhandari covers pathology, immunology, medical microbiology, cell biology, neurology, and radiology. She holds a bachelor’s degree in molecular biophysics and biochemistry and in sociology from Yale University, a master’s in public health/infectious diseases from the University of California, Berkeley, and a PhD in infectious disease immunology from the University of California, San Diego.

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